- Second generation β-elemene nitric oxide derivatives with reasonable linkers: potential hybrids against malignant brain glioma
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Elemene is a second-line broad-spectrum anti-tumour drug that has been used in China for more than two decades. However, its main anti-tumour ingredient, β-elemene, has disadvantages, including excessive lipophilicity and relatively weak anti-tumour effic
- Bai, Renren,Zhu, Junlong,Bai, Ziqiang,Mao, Qing,Zhang, Yingqian,Hui, Zi,Luo, Xinyu,Ye, Xiang-Yang,Xie, Tian
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p. 379 - 385
(2022/01/20)
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- Synthesis of lathyrane diterpenoid nitrogen-containing heterocyclic derivatives and evaluation of their anti-inflammatory activities
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As our ongoing work on lathyrane diterpenoid derivatization, three series of lathyrane diterpenoid derivatives were designed and synthesized based combination principles, including pyrazole, thiazole and furoxan moieties. Biological evaluation indicated t
- Wang, Wang,Xiong, Liangliang,Li, Yutong,Song, Zhuorui,Sun, Dejuan,Li, Hua,Chen, Lixia
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- Aurovertin B derivative as well as preparation method and application thereof
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The invention provides an aurovertin B derivative, a preparation method of the aurovertin B derivative, and an application of the aurovertin B derivative in the preparation of a medicine for treatingtriple negative breast cancer. The polarity of the aurov
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- Design, synthesis and apoptosis-related antiproliferative activities of chelidonine derivatives
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To get chelidonine derivatives with enhanced antiproliferative activity and selectivity, a series of nitric oxide donating derivatives (10a-f and 11a-j) were designed, synthesized and biologically evaluated. Compared with chelidonine, these compounds exhibited lower IC50 values against human hepatoma cells HepG2, breast cancer cells MCF-7, colon cancer cells HCT-116, as well as leukemia cells K562. Compound 11j displayed the strongest antiproliferative activity with IC50 values of 3.91, 6.90, 4.36 and 1.12 μM against the above four cells, respectively. Nevertheless, it showed an IC50 value >40 μM against human peripheral blood mononuclear cells (PBMCs), which demonstrated high selectivity between normal and cancer blood cells. In further mechanism studies, 11j showed the capability to induce K562 cells apoptosis, S phase cell cycle arrest and mitochondrial membrane potential disorder. Besides, 11j was found to be effective in promoting the expression of proapoptotic protein Bad and suppressing the expression of anti-apoptotic proteins Bcl-xL, catalase, survivin, claspin and clusterin.
- Cheng, Keguang,Gao, Xiang,Hu, Xu,Hua, Huiming,Huang, Xueyan,Li, Dahong,Li, Haonan,Li, Zhanlin,Liu, Lilin,Xu, Fanxing
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- Synthesis of cucurbitacin B derivatives as potential anti-hepatocellular carcinoma agents
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Cucurbitacin B shows potent activity against tumor cells, but its high toxicity limits its application in the clinic. A series of cucurbitacin B derivatives was synthesized and evaluated for their anti-hepatocellular carcinoma (HCC) activities against the HepG-2 cell line. These compounds were also tested for their toxicity against the L-O2 normal cell line. The compound with the most potential, 10b, exhibited potent activity against the HepG-2 cell line with an IC50 value of 0.63 μM. Moreover, compound 10b showed the highest TI value (4.71), which is a 14.7-fold improvement compared to its parent compound cucurbitacin B. A preliminary molecular mechanism study of 10b indicated that 10b could inhibit P-STAT3 to induce the activation of mitochondrial apoptotic pathways. An in vivo acute toxicity study indicated that the compound 10b has preferable safety and tolerability compared with cucurbitacin B. These findings indicate that compound 10b might be considered as a lead compound for exploring effective anti-HCC drugs.
- Ge, Weizhi,Chen, Xinyi,Han, Fangzhi,Liu, Zhongquan,Wang, Tianpeng,Wang, Mengmeng,Chen, Yue,Ding, Yahui,Zhang, Quan
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- Discovery of novel antitumor nitric oxide-donating β-elemene hybrids through inhibiting the PI3K/Akt pathway
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A series of novel furoxan-based NO-donating β-elemene hybrids were designed and synthesized to improve the anticancer efficacy of natural β-elemene. The bioassay results indicated that all of the target compounds exhibited significantly improved antiproliferative activities against three cancer cell lines (SGC-7901, HeLa and U87) compared to parent compound β-elemene. Interestingly, these compounds displayed excellent sensitivity to U87?cells with IC50 values ranging from 173 to 2?nM. Moreover, most compounds produced high levels of NO in?vitro, and the antitumor activity of 11a in U87?cells was markedly attenuated by an NO scavenger (hemoglobin or carboxy-PTIO). Further mechanism studies revealed that 11a caused the G2 phase arrest of the cell cycle and induced apoptosis of U87?cells by preventing the activation of the PI3K/Akt pathway. Moreover, 11a significantly suppressed the tumor growth in H22 liver cancer xenograft mouse model with a tumor inhibitory ratio (TIR) of 64.8%, which was superior to that of β-elemene (TIR, 49.6%) at the same dose of 60?mg/kg. Together, the remarkable biological profiles of these novel NO-donating β-elemene derivatives may make them promising candidates for the intervention of human cancers.
- Chen, Jichao,Wang, Tianyu,Xu, Shengtao,Zhang, Pengfei,Lin, Aijun,Wu, Liang,Yao, Hequan,Xie, Weijia,Zhu, Zheying,Xu, Jinyi
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p. 414 - 423
(2017/05/04)
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- Synthesis and biological evaluation of nitric oxide-releasing hybrids from gemcitabine and phenylsulfonyl furoxans as anti-tumor agents
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A series of novel hybrids 10a-m were designed and synthesized by coupling phenylsulfonyl furoxans with gemcitabine through various diols or alcohol amine linkers, and their biological activities were evaluated in vitro. Most of the hybrids exhibited good to moderate anti-tumor activities, which are associated with NO release. In particular, hybrid 10e showed excellent anticancer activities which were more potent than or comparable to gemcitabine. However, inhibition of nucleoside transport only significantly decreased the inhibitory rates of gemcitabine against HepG2 cells but not 10e, and the inhibitory rates of 10e were partially reduced by pre-treatment with hemoglobin, demonstrating that the anti-tumor activity of 10e might result from the synergic effect of high levels of NO production and gemcitabine fragment. In addition, compound 10ecould apparently induce cell apoptosis by regulating apoptotic relative proteins. Therefore, our novel findings provide a proof of principle in the design of new furoxan/gemcitabine hybrids for the intervention of human cancers.
- Li, Xianghua,Wang, Xuemin,Xu, Chenjun,Huang, Junkai,Wang, Chengniu,Wang, Xinyang,He, Liqin,Ling, Yong
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p. 1130 - 1136
(2015/06/25)
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- Novel nitric oxide-releasing derivatives of brusatol as anti-inflammatory agents: Design, synthesis, biological evaluation, and nitric oxide release studies
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Brusatol, a biologically active natural product, was modified in four distinct positions through the covalent attachment of a furoxan moiety, which acts as a nitric oxide (NO) donor. Forty derivatives were synthesized and evaluated for their inhibitory effects on excess NO biosynthesis in activated macrophages. Among them, compound 75 demonstrated inhibition (IC50= 0.067 μM) comparable to that of brusatol but were less cytotoxic. More importantly, even at very low doses (2 μmol/kg/day), compound 75 also showed substantial inhibitory efficacy against chronic obstructive pulmonary disease (COPD)-like inflammation in the mouse model induced by cigarette smoke (CS) and lipopolysaccharide (LPS). Particularly, this compound was over 100-fold less toxic (LD50> 3852 μmol/kg) than brusatol and could be a promising lead for further studies. Notably, the improved properties of this derivative are associated with its NO-releasing capability.
- Tang, Weibin,Xie, Jianlin,Xu, Song,Lv, Haining,Lin, Mingbao,Yuan, Shaopeng,Bai, Jinye,Hou, Qi,Yu, Shishan
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p. 7600 - 7612
(2015/01/09)
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- Synthesis and bioactivity of furoxan-based nitric oxide-releasing colchicine derivatives as anticancer agents
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A series of novel nitric oxide-donating colchicine derivatives (9a-j) were synthesized by coupling furoxan with N-methyl colchiceinamide through an appropriate spacer arm and their cytotoxicity against four human cancer cell lines in vitro were evaluated by MTT method. It was found that many of the derivatives displayed significant activity, particularly, compound 9f showed more potent cytotoxic activities than colchicine.
- Shen, Li Hong,Wang, Sheng Li,Li, Hong Yu,Lai, Yi Sheng,Liu, Li Jie
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p. 3294 - 3296
(2013/04/24)
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- Synthesis and evaluation of furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline as anticancer and multidrug resistance reversal agents
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Multidrug resistance in tumor cells poses a major obstacle to efficient chemotherapy. Several types of agents have been recognized as multidrug resistance inhibitors, among which the tetrahydroisoquinolines is the most studied. In current study 16 furoxan-based nitric oxide-releasing derivatives of tetrahydroisoquinoline were synthesized. Their cytotoxic activities and effects in reversing multidrug resistance have been evaluated. The results revealed that these compounds had moderate cytotoxic effects. Compounds 7a-f, 7h, and 7l showed higher cytotoxicities than the rest, but lower than adriamycin on K562 cell line. Compounds 7d, 7f, and 7l exhibited potent MDR reversal activities on K562/A02 cell line. The accumulation assay indicated that compounds 7d, 7f, and 7l significantly increased the intracellular accumulation of rhodamine123 in K562/A02 cells. Furthermore, these three compounds produced high concentrations of NO in K562/A02 cells. Potentially, the high concentrations of NO produced by NO donor moieties will lead to an increased cytotoxicity to K562/A02 cells. Our results suggested that compounds 7d, 7f, and 7l had anticancer effects, as well as multidrug resistance reversal effects.
- Zou, Zhi-Hong,Lan, Xiao-Bu,Qian, Hai,Huang, Wen-Long,Li, Yun-Man
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scheme or table
p. 5934 - 5938
(2011/10/09)
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